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Note that in this prospective study of 208 Chinese patients undergoing coronary artery bypass grafting, levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the saphenous vein graft were elevated among smokers and former smokers, and appeared to be linked to poor late graft patency.

Smoking at least a pack of cigarettes a day for at least 20 years before surgery was associated with imbalanced levels of proteins involved in vascular remodeling after coronary procedures, according to Wang Chunsheng, MD, of Fudan University in Shanghai, China, and colleagues.

The dysregulated protein levels were associated with worse saphenous vein graft patency at 1 and 2 years after the operation.

Although the levels began to normalize after patients quit smoking, they still had not returned to levels seen in nonsmokers even after at least a year, the researchers reported in the January issue of the Annals of Thoracic Surgery.

"Keeping in mind the serious smoking prevalence and the deteriorated benefits after CABG, it is not difficult to understand the socioeconomic value of reducing smoking-related pathologic changes in vein grafts," they wrote.

Chunsheng and colleagues noted that little is known about the expression of the proteins involved in revascularization of the saphenous veins in heavy smokers who undergo CABG.

"As we know, smoking cessation can dramatically reduce the likelihood of revascularization after CABG," they wrote. "Therefore it will be valuable to investigate to determine the ideal length of time before coronary surgical procedures that the patient should quit smoking" so that the protein expression can resume normal levels.

The researchers examined the relationship between heavy smoking and expression of the genes coding for matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and two tissue inhibitors of metalloproteinases -- TIMP-1 and TIMP-2 -- in the saphenous veins of patients undergoing elective CABG.

"Breakdown of the basement membrane by MMP-2 and MMP-9 allows smooth muscle cell migration, leading to the formation of foam cells and atherosclerotic plaques, which contribute to late vein graft failure," the authors explained.

The study included 208 patients, who were divided into six groups according to smoking status:

Nonsmokers (17%)

Current heavy smokers, who smoked at least 20 cigarettes a day for at least 20 years before the operation (22%)

Heavy smokers who had quit less than 3 months before CABG (16%)

Heavy smokers who had quit 3 to 6 months before CABG (13%)

Heavy smokers who had quit 6 to 12 months before CABG (18%)

Heavy smokers who had quit at least 12 months before CABG (14%)

The patients in the six groups were similar with regard to age, sex, and clinical presentation profile. The average ages ranged from 60 to 64, and 94% to 98% of the patients in each group were men.

The researchers measured mRNA and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in samples of the saphenous veins taken at the time of CABG.

Compared with nonsmokers, patients in the other five groups had significantly greater expression of the genes coding MMP-2 and MMP-9 and reduced expression of the genes coding TIMP-1 and TIMP-2 (P<0.05 for all), with similar differences observed in actual protein levels. The disparity was greatest in the current heavy smokers and declined with greater time since quitting.

Even in the patients who had quit smoking the longest, however, gene expression and protein levels had not yet returned to normal, which "illustrates exactly the importance of prompt smoking cessation for patients who will receive CABG," Chunsheng and colleagues wrote.

Smoking status at the time of CABG was not associated with graft patency measured by multidetector spiral CT 1 month after the operation, but differences emerged between the groups over time.

At 1 year, grafts were patent in 92.7% of the nonsmokers and 85.3% to 89.6% of the rest of the patients. At 2 years, graft patency was present in 89.2% of the nonsmokers and 83.1% to 86.3% of the rest of the patients.

In an invited commentary, Shahab Akhter, MD, of the University of Chicago, wrote, "These data provide preliminary evidence that the balance of MMPs and TIMPs in saphenous vein grafts is altered by smoking and could have a role in early pathologic vein graft remodeling leading to graft failure."

The study authors acknowledged that the analysis was limited by the assessment of gene expression and protein levels in saphenous veins before the surgical procedure, which itself can affect graft integrity, and by the use of an almost entirely male patient population.

They said that "our data and findings still need evidence from further prospective clinical studies that have a large cohort and long-term follow-up."

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